Objective: Current asthma guidelines recommend use of inhaled corticosteroids (ICS) in patients with persistent disease. This study was designed to investigate (1) the proportion of patients ...prescribed ICS-containing maintenance treatment who achieve asthma control, (2) determinants of control and (3) how physicians adapt treatment to the level of control. Methods: General practitioners (GPs) and chest physicians (CPs) in France recruited patients consulting for asthma and prescribed an ICS. Over a 2-year follow-up period, asthma symptoms in the previous 3 months and treatments prescribed were documented at each visit. Variables independently associated with asthma control were determined by multiple logistic regression. Results: Data were available for 924 patients recruited by GPs and 455 recruited by CPs. Asthma control was acceptable in only 24% of patients at inclusion, and in 33.6% at the last follow-up visit. Five factors were independently associated with asthma control: age (or time since diagnosis), gender, smoking status, allergic aetiology of asthma and treatment. Most patients (56.3%) were prescribed the same ICS dose regimen at the end of follow-up as at inclusion. The intensity of controller therapy had been increased in only 12.2% of patients unacceptably controlled at inclusion. Conclusions: Asthma was unacceptably controlled in most patients receiving ICS-containing maintenance treatment and remained so during follow-up. Despite this, treatment adaptations by GPs and CPs were very infrequent. This unsatisfactory situation may be improved by adopting a more dynamic approach to tailoring controller therapy to the needs of the patient.
Introduction: Primary spontaneous pneumothorax (PSP) is the presence of air in the pleural space, occurring in the absence of trauma and known lung disease. Standardized expert guidelines on PSP are ...needed due to the variety of diagnostic methods, therapeutic strategies and medical and surgical disciplines involved in its management.Methods: Literature review, analysis of literature according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology; proposals for guidelines rated by experts, patients, and organizers to reach a consensus. Only expert opinions with strong agreement were selected.Results: A large PSP is defined as presence of a visible rim along the entire axillary line between the lung margin and the chest wall and ≥2 cm at the hilum level on frontal chest x-ray. The therapeutic strategy depends on the clinical presentation: emergency needle aspiration for tension PSP; in the absence of signs of severity: conservative management (small PSP), needle aspiration or chest tube drainage (large PSP). Outpatient treatment is possible if a dedicated outpatient care system is previously organized. Indications, surgical procedures and perioperative analgesia are detailed. Associated measures, including smoking cessation, are described.Conclusion: These guidelines are a step towards PSP treatment and follow-up strategy optimization in France.
Objectives Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on ...eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes. Design A modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ≥70% of experts indicated that the outcome was essential for interpreting study results. Setting COPD exacerbation management in France. Participants 34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds. Results 105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation. Conclusions This Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients. Study registration The eo-Delphi project/protocol was registered on 23 January 2018 at https://osf.io/4ahqw/ .
Single Photon Absorption technique with ultraviolet pulsed laser and focused X-ray beam is used to investigate single event transients in pristine AlGaN/GaN Schottky-Gate and MIS-Gate HEMTs. The ...results depend strongly on structure of devices.
Key points
It has been demonstrated in humans that furosemide crosses the blood–brain barrier and blocks activity in the epileptic brain.
In this study, we demonstrated using non‐invasive ...electrophysiological techniques in healthy human subjects that furosemide, a cation‐chloride co‐transporter blocker, orally administered at doses commonly used in the clinic (40 mg), reduces the efficacy of pre‐ and postsynaptic inhibition of soleus motoneurons in the spinal cord.
Furosemide can be a useful tool to detect the intrinsic functioning of inhibitory synapses and to explore if the reduced inhibitory interneuronal activity that probably contributes to spasticity also exists in humans with spinal cord injury.
During neural development in animals, GABAergic and glycinergic neurons are first excitatory, and then become inhibitory in the mature state. This developmental shift is due mainly to strong expression of the cation‐chloride K–Cl cotransporter 2 (KCC2) and down‐regulation of Na–K–Cl cotransporter 1 (NKCC1) during maturation. The down‐regulation of co‐transporter KCC2 after spinal cord transection in animals leads to the depolarising (excitatory) action of GABA and glycine and thus results in a reduction of inhibitory synaptic efficiency. Furosemide, a loop diuretic, has been shown to selectively and reversibly block inhibitory postsynaptic potentials without affecting excitatory postsynaptic potentials in animal spinal neurons. Moreover, this diuretic has been also demonstrated to block the cation‐chloride co‐transporters. Here, we used furosemide to demonstrate changes in spinal inhibitory networks in healthy human subjects. Non‐invasive electrophysiological techniques were used to assess presynaptic inhibition, postsynaptic inhibition and the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons in the spinal cord. Orally administered furosemide, at doses commonly used in the clinic (40 mg), significantly reduced spinal inhibitory interneuronal activity for at least 70 min from intake compared to control experiments in the same subjects while no changes were observed in the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons. The reduction of inhibition was dose‐dependent. Our results provide indirect evidence that reversible changes in the cation‐chloride transport system induce modulations of inhibitory neuronal activity at spinal cord level in humans.
In a context of overexploitation of natural resources, a circular economy and particularly the extraction of resources from secondary sources are essential to sustain a number of key technologies ...including renewable energies. Among secondary sources, the bauxite residue contains critical elements including rare earth elements (REEs) (712 mg/kg). We investigated the use of soft and selective dissolution protocols at mild pH values (2–6) as an alternative to pyro- and hydrometallurgy for the recovery of REEs through ligand-promoted dissolution. This approach depends on the detailed characterization of the waste and the speciation of targeted elements. We assessed dissolution using low-molecular-weight organic acids and their conjugate bases. Citric acid/citrate showed satisfactory dissolution of REEs (up to 50% of light REEs) up to a pH of nearly 5, while tartaric acid/tartrate showed the best dissolution selectivity (enrichment factor up to 21.5 compared to Fe, Al, and Ti). Almost no heavy REEs were dissolved in any of the conditions tested, probably due to the high chemical stability of their bearing phases. Indeed, heavy REEs were found as discrete phosphate particles